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The objective of this review is to examine the connection between osteoporosis and diabetes, compare the underlying causes of osteoporosis in various forms of diabetes, and suggest optimal methods for diagnosing and assessing fracture risk in diabetic patients. This narrative review discusses the key factors contributing to the heightened risk of fractures in individuals with diabetes, as well as the shared elements impacting the treatment of both diabetes mellitus and osteoporosis. Understanding the close link between diabetes and a heightened risk of fractures is crucial in effectively managing both conditions. There are several review articles of meta-analysis regarding diaporosis. Nevertheless, no review articles showed collected and well-organized medications of antidiabetics and made for inconvenient reading for those who were interested in details of drug mechanisms. In this article, we presented collected and comprehensive charts of every antidiabetic medication which was linked to fracture risk and indicated plausible descriptions according to research articles.
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Hipoglucemiantes , Osteoporosis , Humanos , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Hipoglucemiantes/uso terapéutico , Fracturas Óseas/etiología , Diabetes Mellitus , Densidad Ósea , Complicaciones de la Diabetes , Factores de RiesgoRESUMEN
INTRODUCTION: Acromegaly is an endocrine pathology characterized by the overproduction of human growth hormone. The present study aimed to analyze three-dimensional speckle-tracking echocardiography (3DSTE)-derived tricuspid annular (TA) properties in detail in patients with acromegaly and to compare the findings to those of matched healthy controls. METHODS: The present study consisted of 29 patients with acromegaly (mean age: 55.9 ± 14.5 years, 21 males), of which 13 had an active disease. The control population comprised 57 healthy subjects (mean age: 53.2 ± 8.4 years, 38 males). RESULTS: In the presence of acromegaly, left atrial and end-diastolic left ventricular (LV) sizes were dilated, and LV ejection fraction was increased, which was accompanied by thickened interventricular septum and LV posterior wall as compared with matched healthy controls. The presence of grade 1 mitral (MR) and tricuspid (TR) regurgitations were more frequent in acromegaly than in controls, regardless of disease activity. Higher than grade 1 MR/TR was uncommon in acromegaly. The 3DSTE-derived all end-diastolic (2.47 ± 0.27 cm vs. 2.23 ± 0.27 cm; 8.73 ± 1.77 cm2 vs. 6.67 ± 1.40 cm2; 11.56 ± 1.34 cm vs. 10.20 ± 1.10 cm, p < 0.001 for all) and end-systolic (1.97 ± 0.27 cm vs. 1.77 ± 0.28 cm; 6.24 ± 1.61 cm2 vs. 5.01 ± 1.42 cm2; 9.80 ± 1.35 cm vs. 8.72 ± 1.10 cm, p < 0.001 for all) TA diameters, areas, and perimeters proved to be dilated, while TA functional parameters including TA fractional area change (28.77 ± 9.80% vs. 27.64 ± 15.34%, p = 0.720) and fractional shortening (20.60 ± 9.08% vs. 20.51 ± 8.81%, p = 0.822) were normal in acromegaly regardless of whether acromegaly was active or not. RA volumes respecting the cardiac cycle were dilated in acromegaly as compared with those of healthy controls regardless of disease activity and were associated with respective changes in TA dimensions. CONCLUSIONS: In the presented acromegaly patients, significant TA dilation with preserved function could be detected regardless of disease activity. RA volumes and TA dimensions are correlated in acromegaly.
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Environmental exposures may have endocrine disruptor (ED) effects, e.g., a role for halogenated hydrocarbon chlorobenzenes in increasing vasopressin (AVP), oxytocin (OT) secretion and, in association, anxiety and aggression in male rats has been shown. Our aim is to investigate whether 1,2,4-trichlorobenzenehexachlorobenzene= 1:1 (mClB) treatment of female rats also shows ED effects and reproductive biology differences, and whether AVP may have a mediator role in this? Female Wistar rats were treated (0.1; 1.0; 10.0 µg/bwkg/day) with mClB (by gastrictube) and then 30; 60; 90 days after treatment anxiety (open field test) and aggressive (resident intruder test) behaviors AVP, OT concentrations from blood plasma samples were detected by radioimmunoassay on 30; 60; 90 days. Treated female rats were mated with untreated males. Mating success, number of newborn and maternal aggression on the neonates were monitored. Results showed that AVP, OT levels; and anxiety, aggressive behaviors; and mothers' aggression towards their offspring increased significantly in relation to the duration and the dose of mClB treatment. But mating propensity and number of offspring decreased. Patterns of AVP, OT release and anxiety, aggression behaviors, and reproductive-related behaviors were correlated. Consistent with the literature, our studies confirmed the role of AVP and OT in different behavioral effects.
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Agresión , Ansiedad , Disruptores Endocrinos , Oxitocina , Animales , Femenino , Masculino , Embarazo , Ratas , Agresión/efectos de los fármacos , Agresión/fisiología , Animales Recién Nacidos , Arginina Vasopresina/sangre , Clorobencenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Hexaclorobenceno/sangre , Conducta Materna/efectos de los fármacos , Conducta Materna/fisiología , Oxitocina/sangre , Ratas Wistar , Reproducción/efectos de los fármacos , Reproducción/fisiología , Conducta Sexual Animal/efectos de los fármacos , Conducta Sexual Animal/fisiologíaRESUMEN
Acromegaly is an uncommon systematic endocrine disease caused by the hypersecretion of human growth hormone and, consequently, of insulin-like growth factor-1 during adulthood. Acromegaly could cause a typical cardiomyopathy characterized by left ventricular hypertrophy associated with diastolic dysfunction, which later could progress to systolic dysfunction. Moreover, some valvular and vascular abnormalities are also associated with acromegaly. This present review aims to summarize available information regarding acromegaly-associated abnormalities in myocardial, valvular, and vascular structural and functional properties and their relationship to disease activity and treatment options.
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INTRODUCTION: Acromegaly is a chronic endocrine disorder, which produces a significant amount of human growth hormone and consequently insulin-like growth factor in adulthood due to a tumor in the pituitary gland. If left untreated, it can have a significant effect on the cardiovascular system. It is also known that elite sport activity is also associated with physiologic cardiac transformation, the so-called athletes' heart, in which volumetric and functional adaptation of the heart cavities can be observed. OBJECTIVE: In accordance with the above facts, the question may rightly arise as to what differences can be observed in left ventricular morphology and function in acromegaly, and what similarities and dissimilarities do the obtained results show compared to the values of healthy non-athlete adults compared to the values of the left ventricle of young elite athletes. METHOD: The present study comprised 21 elite athletes playing high dynamic sports (mean age: 31.2 ± 6.4 years, 13 males) and 18 acromegaly patients (mean age: 47.9 ± 8.9 years, 9 males). Their results were compared to those of 22 negative controls (mean age: 47.7 ± 10.6 years, 13 males). RESULTS: Left ventricle is dilated, but its function is preserved in both elite athletes and patients with acromegaly. While increased longitudinal and circumferential left ventricular strains could be seen in elite athletes primarily due to the more pronounced contractility of left ventricular apical segments, increased radial left ventricular strain was detected in acromegaly due to increased function of the left ventricular basal region. Left ventricular rotational mechanics show different patterns as well: while basal left ventricular rotation is decreased in elite athletes, apical left ventricular rotation showed a reduction leading to the significant deterioration of left ventricular twist in acromegaly. CONCLUSION: Both elite athletes playing high dynamic sports and acromegaly patients have dilated left ventricle, more pronounced regional left ventricular contractility and left ventricular rotational abnormalities with differences in nature and extent of these alterations as compared to those of non-sporting healthy subjects. Orv Hetil. 2023; 164(8): 308-316.
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Acromegalia , Ecocardiografía Tridimensional , Deportes , Adulto , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Acromegalia/diagnóstico por imagen , Acromegalia/complicaciones , Ecocardiografía/métodos , Ecocardiografía Tridimensional/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Deportes/fisiología , Función Ventricular Izquierda/fisiología , FemeninoRESUMEN
Nine Hungarian medical societies have developed a consensus recommendation on the preferred normal range of vitamin D, the dose of vitamin D supplementation and the method of administration. They summarized the clinical conditions and diseases the development of which may be associated with vitamin D deficiency (VDD). VDD is extremely common in Hungary, especially in late winter. The lower limit of the recommended normal range is 75 nmol/l, although the clinical significance of deficiency is evident mainly at values below 50 nmol/l, but since vitamin D supplementation at the recommended dose is safe, it is worthwhile for everyone to reduce the health risk associated with VDD. The aim of vitamin D supplementation is to prevent deficiency. The recommended normal range is 75125 nmol/l, above which there is no clear benefit of vitamin D supplementation. To maintain the normal range, a daily intake of 2000 IU in adults is recommended during the UV-B radiation-free period. Vitamin D supplementation is also recommended for children during the same periods and conditions as for adults, but the dose varies with age. In adults, vitamin D3 supplementation at daily, weekly and monthly intervals is equally effective and safe. In severe deficiency, a loading dose is recommended, followed by maintenance supplementation. In addition to the wellknown skeletal, immunological and oncological effects of VDD, more and more data support unfavorable gyneco- logical and obstetric effects. The process of building the consensus has met the requirements of the latest Delphi criteria.
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Vitamina D , Vitaminas , Adulto , Niño , Humanos , HungríaRESUMEN
Reduced secretion of one or more of the hormones normally produced by the pituitary gland is called hypopituitarism, which is a rare and frequently underdiagnosed condition. Hypopituitarism can be present at birth called congenital or may develop due to acquired causes like tumor, infection, infiltration, vascular or other causes. Symptoms of hypopituitarism are highly dependent on which hormones are insufficient. The present prospective study was designed to test whether treated hypopituitarism is associated with changes in 3DSTE-derived LV strains in patients without known cardiovascular disorder. We investigated 38 patients with treated hypopituitarism who were in sinus rhythm (57.0±13.6 years, 19 males), 6 patients were excluded from the study due to inferior image quality. The remaining patient group consisted of 16 patients with congenital hypopituitarism and 16 patients with acquired form of hypopituitarism. Their results were compared to age- and gender-matched controls (mean age: 55.3±4.7 years, 14 males). Out of the 32 patients with hypopituitarism, 30 patients had growth hormone deficiency, 27 patients had central adrenal insufficiency, 12 patients had central hypothyroidism, 12 patients had hypogonadotropic hypogonadism and 5 patients had diabetes insipidus. Only LV longitudinal and area strains proved to be significantly increased in patients with hypopituitarism, other LV strains did not differ between patients and controls. No significant differences could be confirmed in LV strains between patients with congenital and acquired hypopituitarism. It could be concluded that longitudinal LV strains are increased in both congenital and acquired treated hypopituitarism.
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Inflammatory bowel diseases (IBD) are chronic, immune-mediated disorders, which affect the gastrointestinal tract with intermittent ulceration. It is increasingly clear that neutrophil extracellular traps (NETs) seem to have a role in IBD; however, the associated pathogenesis is still not known. Furthermore, several conventional therapies are available against IBD, although these might have side effects. Our current study aimed to investigate the effects of hydrogen sulfide (H2S) treatment on NETs formation and on the expression of inflammatory mediators in experimental rat colitis. To model IBD, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was administered intracolonically (i.c.) to Wistar-Harlan male rats. Animals were treated (2 times/day) with H2S donor Lawesson's reagent per os. Our results showed that H2S treatment significantly decreased the extent of colonic lesions. Furthermore, the expression of members of NETs formation: peptidyl arginine deiminase 4 (PAD4), citrullinated histone H3 (citH3), myeloperoxidase (MPO) and inflammatory regulators, such as nuclear transcription factor-kappa B (NF-κB) and high-mobility group box 1 (HMGB1) were reduced in H2S treated group compared to TNBS. Additionally, H2S donor administration elevated the expression of ubiquitin C-terminal hydroxylase L1 (UCHL-1), a potential anti-inflammatory mediator. Taken together, our results showed that H2S may exert anti-inflammatory effect through the inhibition of NETs formation, which suggests a new therapeutic approach against IBD.
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Antiinflamatorios/farmacología , Colitis/tratamiento farmacológico , Trampas Extracelulares/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , FN-kappa B/metabolismo , Ácido Trinitrobencenosulfónico/toxicidad , Animales , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Gasotransmisores/farmacología , Mediadores de Inflamación/metabolismo , Masculino , FN-kappa B/genética , Ratas , Ratas Wistar , Transducción de SeñalRESUMEN
Introduction: Hypopituitarism is a rare, often underdiagnosed, complex hormonal disease caused by the decreased secretion of one or more hormones in the pituitary gland. The present study was designed to assess left ventricular (LV) rotational mechanics in patients with treated hypopituitarism. It was also aimed to find possible differences in these parameters according to the origin of hypopituitarism (congenital vs. acquired). Methods: The present prospective study involved 35 treated patients with hypopituitarism; however, 4 patients had to be excluded due to inferior image quality. The mean age of the remaining 31 cases was 56.3 ± 13.2 years (18 males). The control group consisted of 29 age- and sex-matched healthy volunteers (mean age: 55.3 ± 4.8 years, 14 males). In all cases a complete two-dimensional echocardiography examination was performed followed by three-dimensional speckle-tracking echocardiography. Results: No significant differences could be found in LV volumes between the controls and patients with hypopituitarism and hypopituitary subgroups. LV apical rotation (8.1 ± 5.1° vs. 10.6 ± 3.5°, p < 0.05) and LV twist (11.9 ± 5.3° vs. 15.1 ± 3.8°, p < 0.05) were impaired in the hypopituitary group with normally directed LV rotational mechanics as compared to the healthy controls. However, 13% of patients showed a near absence of LV twist called LV "rigid body rotation" (LV-RBR). There were no significant differences regarding LV apical and basal rotations and twist between acquired and congenital hypopituitary subgroups. Conclusions: Impaired LV apical rotation and twist could be demonstrated in hypopituitarism regardless of its origin. In the present study with small number of patients with hypopituitarism, LV-RBR was present in 13% of cases.
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BACKGROUND: Epidemiological evidence suggests that synchronous or metachronous presentation of breast and thyroid cancers exceeds that predicted by chance alone. The following potential explanations have been hypothesized: common environmental or hormonal factors, oncogenic effect of the treatment for the first cancer, closer follow-up of cancer survivors, shared underlying genetic risk factors. While some cases were found to be related to monogenic disorders with autosomal inheritance, the genetic background of most cases of co-occurring breast and thyroid cancer is thought to be polygenic. METHODS: In this retrospective case-control study we compared the genetic profile of patients with a history of breast cancer (n = 15) to patients with co-occurring breast and thyroid cancer (n = 19) using next generation sequencing of 112 hereditary cancer risk genes. Identified variants were categorized based on their known association with breast cancer and oncogenesis in general. RESULTS: No difference between patients with breast and double cancers was observed in clinical and pathological characteristics or the number of neutral SNPs. The unweighted and weighted number of SNPs with an established or potential association with breast cancer was significantly lower in the group with breast cancer only (mean difference - 0.58, BCa 95% CI [- 1.09, - 0.06], p = 0.029, and mean difference - 0.36, BCa 95% CI [- 0.70, - 0.02], p = 0.039, respectively). The difference was also significant when we compared the number of SNPs with potential or known association with any malignancy (mean difference - 1.19, BCa 95% CI [- 2.27, - 0.11], p = 0.032 for unweighted, and mean difference - 0.73, BCa 95% CI [- 1.32, - 0.14], p = 0.017 for weighted scores). CONCLUSION: Our findings are compatible with the hypothesis of genetic predisposition in the co-occurrence of breast and thyroid cancer. Further exploration of the underlying genetic mechanisms may help in the identification of patients with an elevated risk for a second cancer at the diagnosis of the first cancer.
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Neoplasias de la Mama/genética , Oncogenes/genética , Polimorfismo de Nucleótido Simple/inmunología , Neoplasias de la Tiroides/genética , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Estudios Retrospectivos , Neoplasias de la Tiroides/patologíaRESUMEN
INTRODUCTION AND OBJECTIVE: Acromegaly is a rare, chronic and slowly developing endocrine disorder caused by hypersecretion of human growth hormone and consequently of insulin-like growth factor-1 during adulthood. The present study was conducted to assess mitral annular (MA) size and function between acromegalic patients and age- and gender-matched healthy controls by three-dimensional speckle-tracking echocardiography (3D-STE). It also aimed to examine whether activity of the disease has any effect on MA parameters. METHODS: This study included 27 patients with acromegaly, three of whom were excluded due to inferior image quality. The mean age of the remaining 24 patients was 55.7±14.0 years and seven were male. Complete two-dimensional Doppler echocardiography and 3D-STE were performed in all cases. RESULTS: Significantly increased end-diastolic and end-systolic MA diameter (2.81±0.36 cm vs. 2.44±0.34 cm and 2.00±0.32 cm vs. 1.65±0.37 cm, respectively), area (9.67±2.33 cm2 vs. 7.38±1.93 cm2 and 5.14±1.62 cm2 vs. 3.74±1.19 cm2, respectively) and perimeter (11.76±1.42 cm vs. 10.27±1.33 cm and 8.61±1.23 cm vs. 7.36±1.10 cm, respectively) were demonstrated in acromegalic patients compared with control subjects. MA functional parameters were not significantly altered compared to those of healthy individuals. CONCLUSIONS: MA dilation could be seen in acromegaly regardless of its activity. Acromegaly is not associated with MA functional impairment.
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Acromegalia , Ecocardiografía Tridimensional , Acromegalia/diagnóstico por imagen , Adulto , Anciano , Ecocardiografía , Ecocardiografía Doppler , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagenRESUMEN
Acromegaly and diabetes mellitus (DM) separately are associated with cardiovascular alterations and modified left ventricular (LV) deformation, which can be quantitatively assessed by three-dimensional speckle-tracking echocardiography (3DSTE). The present study aimed to assess the relationship between LV deformation and twist in the presence of DM in acromegaly. Thirty-seven acromegaly patients were involved in the study, but due to insufficient image quality 13 have to be excluded from analysis. Therefore, the present study comprised 24 acromegaly patients, from which 5 had DM. Their data was compared to 35 age- and gender matched healthy controls. Complete two-dimensional Doppler echocardiography extended with 3DSTE were performed in all patients and controls. Only non-diabetic acromegaly cases had increased global and mean segmental LV radial strain, diabetic acromegaly patients had similar LV radial strain as compared to that of healthy subjects. Other LV strain parameters did not show any difference between diabetic and non-diabetic acromegaly patients. While LV basal rotation was similar among the groups, LV apical rotation was reduced in both diabetic and non-diabetic patients as compared to healthy subjects. However, diabetic acromegaly patients had tendentiously higher values. The ratio of absence of LV twist called as LV rigid body rotation was similar between the groups examined. Diabetes mellitus deteriorates left ventricular deformation in acromegaly.
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Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gastrointestinal tract. Since the treatment of IBD is still an unresolved issue, we designed our study to investigate the effect of a novel therapeutic target, sigma-1 receptor (σ1R), considering its ability to activate antioxidant molecules. As a model, 2,4,6-trinitrobenzenesulfonic acid (TNBS) was used to induce colitis in Wistar-Harlan male rats. To test the beneficial effects of σ1R, animals were treated intracolonically (i.c.): (1) separately with an agonist (fluvoxamine (FLV)), (2) with an antagonist of the receptor (BD1063), or (3) as a co-treatment. Our results showed that FLV significantly decreased the severity of inflammation and increased the body weight of the animals. On the contrary, simultaneous treatment of FLV with BD1063 diminished the beneficial effects of FLV. Furthermore, FLV significantly enhanced the levels of glutathione (GSH) and peroxiredoxin 1 (PRDX1) and caused a significant reduction in 3-nitrotyrosine (3-NT) levels, the effects of which were abolished by co-treatment with BD1063. Taken together, our results suggest that the activation of σ1R in TNBS-induced colitis through FLV may be a promising therapeutic strategy, and its protective effect seems to involve the antioxidant pathway system.
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Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (σ1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of σ1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar-Harlan rats were used to model colitic inflammation through the administration of TNBS. To investigate the effects of σ1R, Fluvoxamine (FLV, σ1R agonist) and BD1063 (σ1R antagonist) were applied via intracolonic administration to the animals once a day for three days. Our radioligand binding studies indicated the existence of σ1Rs as [3H](+)-pentazocine binding sites, and FLV treatment increased the reduced σ1R maximum binding capacity in TNBS-induced colitis. Furthermore, FLV significantly attenuated the colonic damage, the effect of which was abolished by the administration of BD1063. Additionally, FLV potentially increased the expression of ubiquitin C-terminal hydrolase ligase-1 (UCHL-1) and the levels of endothelial nitric oxide synthase (eNOS), and decreased the levels of interleukin-6 (IL-6) and inducible NOS (iNOS) expression. In summary, our study offers evidence for the anti-inflammatory potential of FLV and σ1R in experimental colitis, and our results present a promising approach to the development of new σ1R-targeted treatment options against IBD.
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Colitis/etiología , Colitis/metabolismo , Interleucina-6/metabolismo , Receptores sigma/metabolismo , Transducción de Señal , Ácido Trinitrobencenosulfónico/efectos adversos , Ubiquitina Tiolesterasa/metabolismo , Animales , Colitis/patología , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Fluvoxamina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hemo Oxigenasa (Desciclizante)/metabolismo , Mediadores de Inflamación/metabolismo , Ligandos , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Peroxidasa/metabolismo , Unión Proteica , Ratas , Receptores sigma/agonistas , Receptores sigma/genética , Índice de Severidad de la Enfermedad , Receptor Sigma-1RESUMEN
INTRODUCTION: Acromegaly is a relatively rare chronic hormonal disease resulting in disfigurement. In 90% of cases, acromegaly is caused by a benign pituitary monoclonal human growth hormone-secreting tumor. The aim of the present study was to determine the presence of left ventricular (LV) deformation abnormalities using three-dimensional speckle-tracking echocardiography in a group of acromegalic patients. METHODS: Thirty-eight acromegalic patients were involved in the study. Thirteen patients were excluded due to inadequate image quality. The mean age of the remaining patients was 57.2±13.6 years and seven were male. Their data were compared to an age- and gender-matched control population, which consisted of 34 healthy volunteers (mean age: 52.7±4.9 years, 15 male). RESULTS: Global and mean segmental LV radial strain (RS) (33.2±13.4% vs. 25.2±10.8%, p=0.01 and 36.0±12.1% vs. 28.2±10.0%, p=0.009, respectively) proved to be significantly higher in acromegaly compared to controls. Active acromegalic patients had significantly higher global and mean segmental LV-RS (35.5±14.4% vs. 25.2±10.8%, p=0.03 and 37.9±13.3% vs. 28.2±10.0%, p=0.03, respectively) compared to controls. Between the active and inactive acromegaly groups, only basal LV circumferential strain (-30.2±4.8% vs. -26.7±4.1%, p=0.02) was found to be significantly different. CONCLUSION: The presented clinical, demographic, therapeutic and echocardiographic features demonstrate that active acromegaly is associated with enhanced LV RS as compared to healthy controls and those with inactive acromegaly.
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Acromegalia/fisiopatología , Ecocardiografía Tridimensional/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Voluntarios Sanos , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Función Ventricular/fisiologíaRESUMEN
BACKGROUND: Acromegaly is a chronic, rare hormonal disease associated with major cardiovascular co-morbidities. The disease, in the majority of the cases, is caused by a benign human growth hormone (hGH) secreting adenoma. Cardiovascular involvement is especially common in acromegalic patients from the most common hypertension to cardiomyopathy. Left ventricular hypertrophy and myocardial fibrosis are considered common findings in acromegalic cardiomyopathy, which might result in severe heart failure at end-stages. It was set out to quantify right atrial (RA) morphology and function in a group of acromegalic patients using three-dimensional (3D) speckle-tracking echocardiography (3DSTE). METHODS: The study comprised 30 patients from which 8 patients were excluded due to inadequate image quality. Mean age of the remaining acromegaly patients were 53.7±14.5 years (7 males). In the control group 44 healthy adults were enrolled (mean age: 50.7±12.6 years, 15 males). In each case, complete two-dimensional Doppler echocardiography was performed followed by 3DSTE. RESULTS: All three RA volumetric parameters (Vmax, Vmin, VpreA) were significantly higher in case of acromegaly compared to the healthy controls. Strain analysis revealed that RA function may be enhanced in acromegalic patients, which is more notable in case of active acromegaly. Numerous independent strain parameters had significant correlations with different hormonal variables in the active acromegaly group. These correlations were not present in the inactive acromegaly subgroup. CONCLUSIONS: Acromegaly has a profound effect on RA function and with proper treatment these changes partly seem to be reversible.
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PURPOSE: Multiple endocrine neoplasia type 1 is a rare tumor syndrome caused by germline mutations of MEN1 gene. Phenotype varies widely, and no definitive correlation with the genotype has been observed. Mutation-negative patients with MEN1-associated tumors represent phenocopies. By comparing mutation-positive and mutation-negative patients, we aimed to identify phenotype features predictive for a positive genetic test and to evaluate the role of MEN1 mutations in phenotype modulation. METHODS: Mutation screeening of MEN1 gene by Sanger sequencing and assessment of clinical data of 189 consecutively enrolled probands and relatives were performed at our national and European Reference Center. Multiple ligation probe amplification analysis of MEN1 gene and Sanger sequencing of CDKN1B were carried out in clinically suspicious but MEN1-negative cases. RESULTS: Twenty-seven probands and twenty family members carried MEN1 mutations. Five mutations have not been described earlier. Pronouncedly high number of phenocopies (>70%) was observed. Clinical suspicion of MEN1 syndrome emerged at significantly earlier age in MEN1-positive compared to MEN1-negative probands. Gastroenteropancreatic neuroendocrine tumors developed significantly earlier and more frequently in carriers compared to non-carriers. Probands with high-impact (frameshift, nonsense, large deletions) mutations, predicted to affect menin function significantly, developed GEP-NETs more frequently compared to low-impact (inframe and missense) mutation carriers. CONCLUSIONS: MEN1 phenocopy is common and represents a significant confounder for the genetic testing. GEP-NET under 30 years best predicted a MEN1 mutation. The present study thus confirmed a previous proposal and suggested that GEP-NET under 30 years should be considered as a part of the indication criteria for MEN1 mutational analysis.
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Neoplasia Endocrina Múltiple Tipo 1/genética , Proteínas Proto-Oncogénicas/genética , Adulto , Edad de Inicio , Anciano , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Humanos , Hungría/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/epidemiología , Mutación , Penetrancia , Estudios RetrospectivosRESUMEN
Homeostatic disruptor agents, and endocrine disruptor compounds (EDC) specifically, can originate from agricultural and industrial chemicals. If they modify the adaptation of living organisms as direct (e.g., by altering hormone regulation, membrane functions) and/or indirect (e.g., cell transformation mechanisms) factors, they are classified as EDC. We aimed to examine the potential endocrine-disrupting effects of phenylurea herbicides (phenuron, monuron, and diuron) on the oxytocin (OT) and arginine-vasopressin (AVP) release of neurohypophysis cell cultures (NH). In our experiments, monoamine-activated receptor functions of neurohypophyseal cells were used as a model. In vitro NH were prepared by enzymatic (trypsin, collagenase) and mechanical dissociation. In the experimental protocol, the basal levels of OT and AVP were determined as controls. Later, monoamine (epinephrine, norepinephrine, serotonin, histamine, and dopamine) activation (10-6 M, 30 min) and the effects of phenylurea (10-6 M, 60 min) alone and in combination (monoamines 10-6 M, 30 min + phenylureas 10-6 M, 60 min) with monoamine were studied. OT and AVP hormone contents in the supernatant media were measured by radioimmunoassay. The monoamine-activated receptor functions of neurohypophyseal cells were modified by the applied doses of phenuron, monuron, and diuron. It is concluded that the applied phenylurea herbicides are endocrine disruptor agents, at least in vitro for neurohypophysis function.
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Uron herbicides polluting the environment represent a serious concern for environmental health and may be regarded as endocrine-disrupting compounds (EDCs), which influence the regulation of human homeostasis. We aimed to investigate the effect of EDC urons (phenuron: PU, monuron: MU, and diuron: DU) and chlorobenzenes on the basal release of the adrenocorticotropic hormone (ACTH), which is a part of the adenohypophysis-adrenocortical axis. Hormone secretion in the presence of EDC was studied in two cell types: normal adenohypophysis cells (AdH) and cells of prolactinomas (PRLOMA). PRLOMA was induced in female Wistar rats by subcutaneously injecting them with estrone acetate for 6 months. AdH and PRLOMA were separated from treated and untreated experimental animals, dissociated enzymatically and mechanically in order to create monolayer cell cultures, which served as an experimental in vitro model. We investigated the effects of ED agents separately and in combination on ACTH and prolactin (PRL) release through the hypophyseal-adrenal axis. Hormone determination was carried out by the luminescent immunoassay and the radioimmunoassay methods. Our results showed that (1) uron agents separately did not change ACTH and PRL release in AdH culture; (2) ACTH secretion in arginine vasopressin- (AVP-) activated AdH cells was significantly increased by EDC treatment; (3) ED agents increased the basal hormone release (ACTH, PRL) in PRLOMA cells; and (4) EDC exposure increased ACTH release in AVP-activated PRLOMA cells. We conclude that the herbicides PU, MU, and DU carry EDC effects and show human toxicity potential.
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INTRODUCTION: Acromegaly is a chronic and disfiguring hormonal disease caused by a benign growth hormone-secreting pituitary adenoma in most of the cases. The objective of this study was to investigate three-dimensional (3D) speckle tracking echocardiography (3DSTE)-derived left atrial (LA) volumetric and functional properties in patients with acromegaly. It was also examined whether the activity of acromegaly is associated with further alterations in these LA parameters. METHODS: A total of 23 patients with acromegaly were involved in this study. Due to inadequate image quality, 4 patients were excluded from the 3DSTE analysis. The mean age of the remaining acromegalic subjects was 58.5 ± 13.1 years (7 males). The control group consisted of 21 age- and gender-matched healthy subjects (mean age 51.8 ± 10.3 years, 10 males). RESULTS: Maximum (44.8 ± 12.7 mL vs 78.7 ± 25.4 mL, P < .05), minimum (24.1 ± 9.0 mL vs 44.5 ± 15.5 mL, P < .05), and preatrial contraction (35.5 ± 11.2 mL vs 66.0 ± 22.8 mL, P < .05) LA volumes were significantly different between all acromegaly patients compared with controls. Increased peak global and mean segmental radial and 3D strains and decreased LA circumferential strain (CS) could be detected in all acromegaly patients as compared to healthy subjects. Significant correlation could be detected between insulin-like growth factor 1 (IGF-1) index and peak superior LA-CS (r = .49, P = .05) in acromegaly. CONCLUSION: Acromegaly is associated with increased LA volumes and changes in LA functional properties.